Drug & supplement interaction

Red Clover + Amitriptyline

Amitriptyline brand name: Elavil.

Minor Interaction
Medically reviewed by · Updated September 2026
The bottom line Minor

Amitriptyline falls into 4 drug categories that Red Clover can interact with; the most serious is rated minor. Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Red Clover and Amitriptyline

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Red Clover interacts with whole categories of medication. Amitriptyline falls into 4 of those categories, so it can interact with Red Clover in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 4

Why this applies to Amitriptyline

Amitriptyline falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Red Clover interacts with.

Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.
In vitro evidence shows that red clover inhibits CYP1A2. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine, a CYP1A2 probe substrate.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for amitriptyline (Elavil). One of the liver enzymes that helps break it down is called CYP1A2. In a test tube, red clover's isoflavones can slow that enzyme a little. If that happened in your body, amitriptyline could clear more slowly and build up, which might mean more of its usual side effects like drowsiness, dry mouth, constipation, blurry vision, or feeling lightheaded when you stand.

But here's the reassuring part: this concern is mostly theoretical. When researchers actually tested standardized red clover in people, it did not change how a similar CYP1A2 drug was handled. So a real-world problem is unlikely. Still, since amitriptyline affects the heart and nervous system, it's worth a quick check with your pharmacist or doctor before adding red clover.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. PubMed
Minor

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

2 of 4

Amitriptyline also falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES.

Theoretically, red clover might increase the levels and clinical effects of drugs metabolized by CYP2C19.
In vitro evidence suggests that red clover weakly inhibits CYP2C19. This interaction has not been reported in humans.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version: your body uses several liver enzymes to break down amitriptyline, and one of them is called CYP2C19. In lab dishes (not in real people), red clover seems to slow that enzyme down a little. If that happened in the body, amitriptyline could clear out more slowly and build up slightly, which in theory might nudge up its usual effects, things like drowsiness, dry mouth, constipation, blurred vision, or feeling lightheaded when you stand.

That said, I don't want to overstate this. This is theoretical, based only on test-tube data, and it hasn't been reported in actual patients. The blocking effect was also weak. Still, it's worth a quick mention to your pharmacist or doctor before combining them, especially if you notice more side effects than usual.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

3 of 4

Amitriptyline also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, red clover might increase levels of drugs metabolized by CYP2C9; however, a small clinical study found no effect.
In vitro evidence suggests that red clover might inhibit CYP2C9. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of tolbutamide, a CYP2C9 probe substrate.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for amitriptyline (Elavil): red clover's plant compounds (isoflavones) have shown, in lab dish studies only, that they might slow down a liver enzyme called CYP2C9, which helps clear part of this medication. If that happened in real life, amitriptyline could build up a bit, possibly nudging up its usual side effects like drowsiness, dry mouth, constipation, or dizziness.

The reassuring part: this is only theoretical. When researchers actually tested red clover in people, it didn't change how the body handled a CYP2C9 test drug. So a real-world problem is unlikely. Still, since everyone's different, it's worth a quick mention to your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

4 of 4

Amitriptyline also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, red clover might increase levels of drugs metabolized by CYP3A4; however, a small clinical study found no effect.
In vitro evidence shows that red clover might inhibit CYP3A4 isoenzymes. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of alprazolam, a CYP3A4 probe substrate.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version: in a test tube, red clover's plant estrogens looked like they might slow down CYP3A4, one of the liver enzymes that helps break down amitriptyline. If that actually happened in the body, amitriptyline could build up a bit and you might notice more of its usual effects, like drowsiness, dry mouth, constipation, or feeling lightheaded when you stand.

But here's the reassuring part: when researchers actually tested standardized red clover in people, it did not change the levels of a similar CYP3A4 drug. So this concern is mostly theoretical and unlikely to cause real trouble. Still, since amitriptyline can be sensitive to changes, it's worth a quick chat with your pharmacist or doctor before adding red clover.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  3. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Red Clover Also Interacts With Other Medications

Red Clover has 44 moderate, 822 minor known drug interactions in our database — the Amitriptyline one above is among them. If you take anything else, check it against the full list below.

Moderate 44 Minor 822 No known interaction 1,964 (incl. Amitriptyline)
Taking anything else?

Check Another of Your Medications Against Red Clover

Covers the 2,830 medications we’ve checked against Red Clover. Pick one to open its full report.

From our Q&A

Questions About Red Clover or Amitriptyline

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Red Clover or Amitriptyline, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Amitriptyline

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline page lists 296 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 17 major · 228 moderate · 51 minor.

From our pharmacist’s overview on the Amitriptyline page

“Amitriptyline (Elavil), an older antidepressant now often prescribed for nerve pain, migraines, and sleep, is one of the drugs I genuinely want patients to be careful with, and 17 of the 296 supplement and herbal ingredients on this list carry a major rating. Most of the serious ones deepen the drowsiness amitriptyline already causes,…”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline interaction page

One more smart check

Taking Red Clover as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,480 real supplement products containing Red Clover, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Red Clover. Your product may carry other ingredients that interact with Amitriptyline too, on top of Red Clover — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Red Clover and Amitriptyline Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Red Clover
Top 25%

#161 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Amitriptyline
Top 5%

#49 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Red Clover

What is Red Clover?

Red Clover
  • Menopause symptoms (hot flashes)
  • High cholesterol
  • Bone health/osteoporosis
  • Skin and hair concerns
  • Women's health

Red clover is a plant rich in isoflavones (plant compounds with weak estrogen-like activity) that is most often used for menopause symptoms like hot flashes. The evidence is mixed and generally weak, with some studies showing modest benefit and others showing none. Because of its hormone-like effects, it's not for everyone—talk with your pharmacist or doctor before trying it, especially if you have a hormone-sensitive condition.

Read the full Red Clover monograph & all interactions
Medication

About Amitriptyline

What Is Amitriptyline Used For?

Brand name: Elavil

Amitriptyline HCL and Amitriptyline Hydrochloride tablets are used to relieve symptoms of depression. Depression that originates from within the body (called endogenous depression) tends to respond better than other types of depression.

See full Amitriptyline drug information
Keep checking

Other Drugs & Red Clover

Browse every other medication we’ve checked against Red Clover — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
44Moderate
822Minor
1,963No known interaction
44 Moderate 822 Minor 1,963 No interaction
Moderate

44 interactions

Minor

822 interactions

Showing 60 of 822 minor interactions — see all 822 on the Red Clover page.

No interaction 1,963 drugs checked — show the list

We also checked Red Clover against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,963 medications checked with no known interaction — see the full Red Clover list.

See the full Red Clover interactions page
See every supplement checked against Amitriptyline, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Red Clover monograph › Uses, safety, and every drug interaction in one place Amitriptyline supplement interactions › Every supplement checked against Amitriptyline, ranked by severity Amitriptyline drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Red Clover and Amitriptyline Together: Common Questions

Can you take Red Clover with Amitriptyline?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 4 interactions listed for Red Clover and Amitriptyline?
Amitriptyline belongs to more than one drug category, and Red Clover interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Red Clover and Amitriptyline interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Amitriptyline and Red Clover?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.